This proposal is a focused and rigorous test of a single hypothesis concerning male sexual function. Preliminary experiments with a novel preparation developed in this laboratory demonstrated that intraurethral stimuli elicited a fully developed ejaculatory-like response (the coitus reflex) in male rats. These findings have prompted a unifying hypothesis which proposes that ejaculation is induced by mechanical and chemical stimulation of the urethra by seminal fluids. The present proposal represents a definitive test of this theory using a multidisciplinary approach. The sensory responses elicited by seminal fluids and chemically inert fluids will be compared in quantitative electrophysiological experiments. The threshold (urethral pressure and flow) for evoking the coitus reflex will be measured to determine if seminal fluids are more stimulatory than chemically inert fluids, a strong indication of chemosensory mechanisms. Multi- and single-unit studies will examine the afferent response to these intraurethral stimuli. The presence of serotonergic paracrine cells have been demonstrated in the urethra sensory processes. This suggestion will be tested by immunohistochemical mapping studies, specific neurotoxic lesions with functional assessment, and pharmacological studies using specific serotonergic agonists and antagonists. Peptidergic afferents have been localized in the urogenital system and physiological studies suggest a role for peptidergic mechanisms in mediating some pelvic functions. The role of peptidergic afferents in the coitus reflux will be examined by immunohistochemical mapping, specific neurotoxic lesions with functional testing, release studies and pharmacological studies using tackykinin agonists.